Biological Data Analysis using InterMine · 2017-11-07 · Biological Data Analysis using InterMine...
Transcript of Biological Data Analysis using InterMine · 2017-11-07 · Biological Data Analysis using InterMine...
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Biological Data Analysis using InterMine
Rachel LyneJulie Sullivan
Josh Heimbach
October 27th 2017
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Workshop Schedule
● Introduction● Walk through interface with hands-on exercises● Analysis workflows● Web services● Questions and detailed use-case
www.flymine.orgwww.humanmine.org
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What is InterMine?
• Data Warehouse• Open Source• Integration of Biological Data• Gos Micklem; Dept of Genetics
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What is InterMine?
• Webapp – user interface
•Data browsing and exploration•Analysis tools•Advanced search interfaces
• API●Perl, Python…...JSON, XML
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Who Uses InterMine?
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Data
FUNCTION
PHENOTYPES
PROTEIN DOMAINS EXPRESSION
INTERACTIONSGENES
PROTEINS
DISEASE
ORTHOLOGUES GWAS
ALLELES
SEQUENCE VARIANTS
GENE ONTOLOGY
PATHWAYS
REGULATION
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Why use InterMine?
● Query across several data sources at once● No need to deal with several data formats● Identifier resolution system● Collate information about items and sets● Common platform to many organisms and type of data● Information without visiting several sites
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InterMine Data IntegrationYour own InterMine:
●Sophisticated build system●Set integration keys
(define equivalence between datasets)●ID resolution system
(old datasets, different identifier systems)●Core library of data loaders●Custom data loaders - own data
Tutorial: www.intermine.org
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Model Organism Data
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The InterMOD Project
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InterMine Accounts
InterMine is free to use without creating an account.
Creating an account allows you to save lists and searches permanently and share lists with your colleagues.
At the moment you have to make a separate account forEach InterMine database
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Using InterMine
SearchExploreAnalyse
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The Web Interface
KeywordSearch
TemplateSearches
QueryBuilder
RegionSearch
ResultsTables
ReportPages
List AnalysisPages
Single Item
List
Inputs
Search InterfacesOutputs
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The Web Interface
KeywordSearch
TemplateSearches
QueryBuilder
RegionSearch
ResultsTables
ReportPages
List AnalysisPages
Single Item
List
Inputs
Search InterfacesOutputs
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Search and Explore
Faceted Keyword Search:
-Specific e.g. pax6, pparg→ Report pages
-Exploratory e.g. Insulin, Diabetes→ Report pages→ Lists
-Filter results by data type
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Data Exploration: report pagesEvery object (item) in InterMine has a report page
● Report pages collate all the data available for that object
● Report pages contain a mixture of tables, search results and graphical displays.
● The tables and graphical displays are interactive
● You can explore data by navigating through links to report pages for related objects.
● Report pages are accessed from keyword searches and results tables.
● Report pages for different InterMines can be configured differently
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Explore: Pax6
Washington NL, Haendel MA, Mungall CJ, Ashburner M, Westerfield M, Lewis SE. - Figure 1 of Washington et al.: "Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation." PLoS Biol 7(11): e1000247. doi:10.1371/journal.pbio.1000247
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Exercise 1: Faceted Search1. Search for one or more of the following in HumanMine:
●PPARG●rs10509540●*diabetes*
2. Filter and create a list:
●Search for *diabetes*●Filter for publications●Make a list of these publications
Note: If you filter for genes note that this is not a comprehensive search for diabetes genes as it does not check functional annotations.
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Exercise2: Exploring a GeneYou are interested in the Human PPARG gene and want to know the following things about it:
1. On which chromosome is PPARG located?
2. Can I access the sequence for the PPARG gene?
3. With which diseases is PPARG associated?
4. In which tissues is PPARG most highly expressed?
5. Does the PPARG protein have any know isoforms?
6. Is there a PPARG orthologue in D. melanogaster?
7. Does this orthologue interact with any other Genes/proteins? Identify the interaction type (genetic/physical)
8. For the interaction with CG3040, what was the original experiment and publication that determined this interaction
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The Web Interface
KeywordSearch
TemplateSearches
QueryBuilder
RegionSearch
ResultsTables
ReportPages
List AnalysisPages
Single Item
List
Inputs
Search Interfaces Outputs
ListUpload
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List Analysis: Uploading a list
● Upload your own lists to InterMine● Powerful identifier resolution system● Convert old identifiers into an up-to-date set
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Exercise 3:Uploading a list:
1. Use FlyMine: navigate to the lists tab and list upload sub- tab
2. Select the example list (leave type and organism as the default values).
3. Click “Create list”.
4. Examine and understand the list page, name and save your list.
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● E2f has matched two genes (duplicates) - in this case you need to decide which of the two genes you want in your list (or both). The action column allows you to do this.
● Two of the identifiers in the list matched the same gene: FBgn0010433 and ato. This is indicated in the direct hits.
● One of the identifiers is a protein identifier (TWIST_DROME). As the associated gene could be identified, this has been added to the list. This is shown under non-gene identifiers.
● Two of the identifiers matched a synonym (rather than a current identifier). As the synonyms matched only one gene, these are automatically added to the list.
Exercise 3:Uploading a list:
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Data Exploration. Lists
• Form a basic “unit” of analysis• Can be uploaded or created from searches• Identifier resolution• All lists have a list analysis page• Provide summary table, widgets and search results• List set operations - union, intersect, subtract• Allow workflows through iterative querying and set operations
• Public lists also available
InterMine allows you to explore data for a whole list of objects
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List Analysis
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Exercise 4: List Analysis: Examine the FlyMine public list: PL FlyTF_putativeTFs (757 genes)
1. In which tissues are these genes most highly expressed?
2. What is the most enriched GO term for this list?
3. How many genes in the list are annotated with this GO term? 4. Note: you could make a sub-list containing only genes from this list annotated with this term by clicking on the matches number
5. Navigate to the MouseMine database to examine the mouse orthologues for this list.
6. How many mouse orthologues are there for this list?
7. Are these mouse genes enriched for any phenotypes?
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Using InterMine
SearchExploreAnalyse
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The Web Interface
KeywordSearch
TemplateSearches
QueryBuilder
RegionSearch
ResultsTables
ReportPages
List AnalysisPages
Single Item
List
Inputs
Search InterfacesOutputs
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Data Analysis: Template Searches
● What other genes are involved in pancreatic function?
● Are there potential targets of pax6 in pancreatic tissue?
● Have these genes been implicated in pancreatic disease?
● What published data is there about these genes?
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Data Analysis: Template Searches
• Pre-defined searches with simple filters• Range from simple searches to more complex searches spanning several data types
• Run with single item or list• Results are returned in sophisticated results tables• Easy to add - just ask
The template searches allow a more refined search than the keyword search and report pages but are still quick and easy to access.
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Many Many Searches…..● Which other genes have this GO annotation?● Are there mutant phenotypes for this gene?● Where is this gene expressed?● What does this gene interact with?● Do any of the interacting genes share the mutant phenotypes?
● Does this gene have a human orthologue with a disease association?
● Have any variants been associated with this gene/disease?
● Which organisms have models for this disease/gene?
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Gene + Tissue Expression → Interactors that are expressed in that tissue
Data Analysis: Template SearchesAre there potential targets of pax6 in pancreatic tissue?
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Data Analysis: Results Tables
• Column summaries• Column sorting• Adding additional columns of data• Filtering• List creation• Export
Results tables allow further interactive analysis of the data through:
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The power of column summaries
● Find the number of unique items in a column● Find the number of items with a particular property● Filter the table for one or more specific properties
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Exercise 5: Template searches:
1. Browse the template searches in FlyMine and HumanMine - try running a few or changing the filters.
2. Use the search box to find template searches for interactions
3. Filter the FlyMine template searches to show only “expression” templates.
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Exercise 6: Using template searches: In our exploration of the PPARG gene we could see that it is Up-regulated in adipose tissue. Use the template searches in HumanMine to answer the following questions:
1. What other genes are up-regulated in adipose tissue according to the array express dataset? Don't forget to add a filter for “UP” expression. Save a list of these genes.
2. Do any of the genes identified in 1. interact with PPARG? Save a listof these genes.
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The Web Interface
KeywordSearch
TemplateSearches
QueryBuilder
RegionSearch
ResultsTables
ReportPages
List AnalysisPages
Single Item
List
Inputs
Search InterfacesOutputs
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Advanced Search:Query Builder
● Build your own Searches
● Modify template searches
● Combine any data:
● And, Or, ● Intersect; Union
The Query Builder is InterMine’s custom query builder,allowing you to create and save your own searches.
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Data Analysis: Query BuilderThree steps to construct a query:
1.Navigate the data model to find the class or attribute you need
2.Add the appropriate constraint (filter) to the class/attribute
3.Decide on the columns you want to view in your results
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Exercise 7: Query Builder: Using HumanMine: we will build a query to show Human genes and OMIM diseases, and then add a further constraint to show genes associated with all types of Diabetes.
1. Start your query from Gene2. Constrain “Organism” to Homo Sapiens3. Add the columns of data we want in our results:
Gene: Primary identifier and Symbol Disease: name
4. Run this search - ‘Show results’.5. Return to the query (Use the “Trail” in the top left) and add a constraint to Disease name for “CONTAINS Diabetes”6. Run the search and save the set of genes
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The Web Interface
KeywordSearch
TemplateSearches
QueryBuilder
RegionSearch
ResultsTables
ReportPages
List AnalysisPages
Single Item
List
Inputs
Search InterfacesOutputs
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Analysis Workflows
Motenko H, Neuhauser SB, O'Keefe M, Richardson JE. MouseMine: a new datawarehouse for MGI. Mamm Genome. 2015 Aug;26(7-8):325-30. doi:10.1007/s00335-015-9573-z. PubMed PMID: 26092688; PubMed Central PMCID:PMC4534495
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Combine Lists
Intersect Union
Subtraction Asymmetric difference
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Exercise 8: Analysis WorkflowsIn exercise 6 we ran a template search, saved a set of genes and fed this set back into another template. In this exercise we will first combine our final set of genes from exercise 6 with our set of diabetes genes from exercise 7.
1. Identify the sets of genes you have created under the lists “view” tab.
2. Use the list set operations available on this page to intersect the listof diabetes genes you created with the query builder with your previous set of genes (genes expressed in adipose tissue that interact with pparg) created in exercise 6.
3. We now want to know if any of these genes have been identified inGWAS studies. Run a template on your intersected list to find this out.
4. Use the column summary to find if any of the GWAS phenotypes are related to diabetes.
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Analysis Workflows
Motenko H, Neuhauser SB, O'Keefe M, Richardson JE. MouseMine: a new datawarehouse for MGI. Mamm Genome. 2015 Aug;26(7-8):325-30. doi:10.1007/s00335-015-9573-z. PubMed PMID: 26092688; PubMed Central PMCID:PMC4534495
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1. We looked at gene expression in adipose tissue and refined this to find gene UP regulatedin this tissue. We saved these as a list – Set A.
Analysis Workflow
RegionSearch
ReportPages
KeywordSearch
UP regulated in adipose tissue
SetATissue → Gene Expression (Array Express E-MTAB-62)
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2. Genes saved as SetA were “plugged in” to a second template to identify if any of these genes are known to interact with Pparg. These genes were saved - SetB
Analysis Workflow
RegionSearch
ReportPages
KeywordSearch
Genes that interact with PPARG
SetAGene + TissueExpression ->Interactors that areExpressed in thattissue SetB
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3. A query built through the query builder identified a set of genes involved in Diabetes -> setC
Analysis Workflow
RegionSearch
ReportPages
KeywordSearch
SetCGenes WITH diabetes
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Analysis Workflow
RegionSearch
ReportPages
Lists
4. A list intersection between setB and setC identified genes expressed in adipose tissue that interact with PPARG that also have some association with diabetes →setD
KeywordSearch SetB
B∩C
Lists:
SetC
SetD
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Analysis Workflow
RegionSearch
ReportPages
Lists
5. ListD contained only one gene but we could explore this further through its report page and through further templates – for example looking at GWAS studies.
KeywordSearch SetB
B∩C
Lists:
SetC
SetD
Gene -->GWAS hit
GWAS studies looking at diabetes/Phenotypes associated with diabetes
Report Page
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The Web Interface
KeywordSearch
TemplateSearches
QueryBuilder
RegionSearch
ResultsTables
ReportPages
List AnalysisPages
Single Item
List
Inputs
Search InterfacesOutputs
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Data Analysis: RegionSearch
The Region Search allows you to search for features that overlap a list of genome coordinates.
● Any or selected genome features can be searched.● Accepts base or interbase coordinates● Region to be searched can be extended upstream and downstream
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Exercise 9: Region Search:
Using FlyMine:
1. Select the example set of regions2. De-select the features and re-select Genes and Regulatory regions
3. Extend the search by 5kb4. Run the search
Examine the results and:
5. Create a list of all genes found.6. Create a list of the regulatory regions found in the first genomic span.
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HELP?● FlyMine - extensive manual and videos under the ‘help’ link. These apply to all InterMine databases
● Each InterMine has it’s own help pages, videos and tutorials
Email Us: Every InterMine page has a ‘questions/comments’ link. Use this if you get stuck - we try and reply within 24 hrs.
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Web Services
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Web ServicesUsing the API, you can:
● Execute an arbitrary query● Discover the set of available templates, and execute one,
supplying it parameter values● Do a keyword (text) search● Upload a batch of identifiers and resolve them to database objects● Create lists, combine them with set operations● Operate in authenticated or non-authenticated (public) mode
Etc… pretty much anything you can do via the web interface
Extensive documentation at www.intermine.org
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Web Services
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Web Services
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Web Services
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Web Services
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Web Services
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Web Services: The basics of a query
3 basic steps:
1. Import service class and create interMine object2. Define “views”: i.e the results output (like “show” in query builder)3. Define constraints
4. Process the results
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Web Services: The basics of a queryAn example using python:
from intermine.webservice import ServiceService= Service("http://www.humanmine.org/humanmine/service")query = service.new_query("Gene")query.add_view("primaryIdentifier", "symbol")query.add_constraint("organism.name", "=", "Homo sapiens", code = "A")query.add_constraint("diseases.name", "CONTAINS", "diabetes", code = "B")for row in query.rows(): print row["primaryIdentifier"], row["symbol"]
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Web Services: The basics of a queryAn example using python:
from intermine.webservice import ServiceService= Service("http://www.humanmine.org/humanmine/service")query = service.new_query("Gene")query.add_view("primaryIdentifier", "symbol")query.add_constraint("organism.name", "=", "Homo sapiens", code = "A")query.add_constraint("diseases.name", "CONTAINS", "diabetes", code = "B")for row in query.rows(): print row["primaryIdentifier"], row["symbol"]
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Web Services: The basics of a queryAn example using python:
from intermine.webservice import ServiceService= Service("http://www.humanmine.org/humanmine/service")query = service.new_query("Gene")query.add_view("primaryIdentifier", "symbol")query.add_constraint("organism.name", "=", "Homo sapiens", code = "A")query.add_constraint("diseases.name", "CONTAINS", "diabetes", code = "B")for row in query.rows(): print row["primaryIdentifier"], row["symbol"]
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Web Services: The basics of a queryAn example using python:
from intermine.webservice import ServiceService= Service("http://www.humanmine.org/humanmine/service")query = service.new_query("Gene")query.add_view("primaryIdentifier", "symbol")query.add_constraint("organism.name", "=", "Homo sapiens", code = "A")query.add_constraint("diseases.name", "CONTAINS", "diabetes", code = "B")for row in query.rows(): print row["primaryIdentifier"], row["symbol"]
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Web Services: The basics of a queryAn example using python:
from intermine.webservice import ServiceService= Service("http://www.humanmine.org/humanmine/service")query = service.new_query("Gene")query.add_view("primaryIdentifier", "symbol")query.add_constraint("organism.name", "=", "Homo sapiens", code = "A")query.add_constraint("diseases.name", "CONTAINS", "diabetes", code = "B")for row in query.rows(): print row["primaryIdentifier"], row["symbol"]
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Web Services: The basics of a queryAn example using perl:
use strict;use warnings;$, = "\t";binmode(STDOUT, 'utf8');no warnings ('uninitialized');use Webservice::InterMine 'http://www.humanmine.org/humanmine';my $query = new_query(class => 'Gene');$query->add_view(qw/ primaryIdentifier symbol/);$query->add_constraint( path => 'Gene.organism.name', op => '=', value => 'Homo sapiens', code => 'A',);$query->add_constraint( path => 'Gene.diseases.name', op => 'CONTAINS', value => 'diabetes', code => 'B',);my $it = $query->iterator();while (my $row = <$it>) { print $row->{'primaryIdentifier'}, $row->{'symbol'}, "\n";}Close
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Web Services: The basics of a queryAn example using perl:
use strict;use warnings;$, = "\t";binmode(STDOUT, 'utf8');no warnings ('uninitialized');use Webservice::InterMine 'http://www.humanmine.org/humanmine';my $query = new_query(class => 'Gene');$query->add_view(qw/ primaryIdentifier symbol/);$query->add_constraint( path => 'Gene.organism.name', op => '=', value => 'Homo sapiens', code => 'A',);$query->add_constraint( path => 'Gene.diseases.name', op => 'CONTAINS', value => 'diabetes', code => 'B',);my $it = $query->iterator();while (my $row = <$it>) { print $row->{'primaryIdentifier'}, $row->{'symbol'}, "\n";}Close
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Web Services: The basics of a queryAn example using perl:
use strict;use warnings;$, = "\t";binmode(STDOUT, 'utf8');no warnings ('uninitialized');use Webservice::InterMine 'http://www.humanmine.org/humanmine';my $query = new_query(class => 'Gene');$query->add_view(qw/ primaryIdentifier symbol/);$query->add_constraint( path => 'Gene.organism.name', op => '=', value => 'Homo sapiens', code => 'A',);$query->add_constraint( path => 'Gene.diseases.name', op => 'CONTAINS', value => 'diabetes', code => 'B',);my $it = $query->iterator();while (my $row = <$it>) { print $row->{'primaryIdentifier'}, $row->{'symbol'}, "\n";}Close
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Web Services: The basics of a queryAn example using perl:
use strict;use warnings;$, = "\t";binmode(STDOUT, 'utf8');no warnings ('uninitialized');use Webservice::InterMine 'http://www.humanmine.org/humanmine';my $query = new_query(class => 'Gene');$query->add_view(qw/ primaryIdentifier symbol/);$query->add_constraint( path => 'Gene.organism.name', op => '=', value => 'Homo sapiens', code => 'A',);$query->add_constraint( path => 'Gene.diseases.name', op => 'CONTAINS', value => 'diabetes', code => 'B',);my $it = $query->iterator();while (my $row = <$it>) { print $row->{'primaryIdentifier'}, $row->{'symbol'}, "\n";}Close
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Web Services: The basics of a queryAn example using perl:
use strict;use warnings;$, = "\t";binmode(STDOUT, 'utf8');no warnings ('uninitialized');use Webservice::InterMine 'http://www.humanmine.org/humanmine';my $query = new_query(class => 'Gene');$query->add_view(qw/ primaryIdentifier symbol/);$query->add_constraint( path => 'Gene.organism.name', op => '=', value => 'Homo sapiens', code => 'A',);$query->add_constraint( path => 'Gene.diseases.name', op => 'CONTAINS', value => 'diabetes', code => 'B',);my $it = $query->iterator();while (my $row = <$it>) { print $row->{'primaryIdentifier'}, $row->{'symbol'}, "\n";}Close
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Web Services: Processing resultsIn Python:
1. Dictionary form2. List3. Result row object
1. for gene in query.results (row = “rr”): print(gene)
2. for gene in query.results(“list”): print(gene[1], gene[2])
3. for gene in query.rows(): print(gene)
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Web Services: Processing resultsIn Perl:
We will use the results_iterator:
Returns a results object that allows you to iterate through the results row by row, in whatever format you choose.
See the online documentation for other ways to process results.
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Web Services: API Tokens
If you need to access your account through the API you needto use an API token. You will need this to create and access your lists.
You can get your API token from your MyMine account:
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Web Services: API Tokens
If you need to access your account through the API you needto use an API token. You will need this to create and access your lists.
You can get your API token from your MyMine account:
from intermine.webservice import Serviceservice = Service("http://www.humanmine.org/humanmine/service", token = "YOUR-API-KEY")
use Webservice::InterMine 'http://www.humanmine.org/humanmine','i1S5MfG1f0Xbd5r2I5u5';
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Templates - pythonfrom intermine.webservice import Serviceservice = Service("http://www.humanmine.org/humanmine/service")
# For a given human disease returns a list of associated or implicated human# genes (source: OMIM)
template = service.get_template('Dis_Gene')
# You can edit the constraint values below# A Disease.name
rows = template.rows( A = {"op": "=", "value": "*Diabetes*"})
for row in rows: print row["genes.primaryIdentifier"], row["genes.symbol"], row["genes.name"], row["name"], \ row["identifier"], row["genes.organism.shortName"]
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Templates - perluse Webservice::InterMine 0.9904 'http://www.humanmine.org/humanmine';
# Description: For a given human disease returns a list of associated or# implicated human genes (source: OMIM)
my $template = Webservice::InterMine->template('Dis_Gene') or die 'Could not find a template called Dis_Gene';
# Use an iterator to avoid having all rows in memory at once.
my $it = $template->results_iterator_with( # A: Disease.name opA => '=', valueA => '*Diabetes*',);
while (my $row = <$it>) { print $row->{'genes.primaryIdentifier'}, $row->{'genes.symbol'}, $row- >{'genes.name'}, $row->{'name'}, $row->{'identifier'}, $row- >{'genes.organism.shortName'}, "\n";}
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Exercise1:
Tutorial1: The basics of a queryTutorial2: Adding constraints to a queryTutorial5: Query resultsTutorial7: Templates
Python:
Perl:http://search.cpan.org/~intermine/Webservice-InterMine-1.0405/lib/Webservice/InterMine/Cookbook.pod
Recipe 1: The bare basicsRecipe 2: Adding constraintsRecipe 5: Dealing with resultsTemplates::Recipe1 : templates
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Exercise2:Re-create the workflow we did using the webapp using eitherPython (recommended) or Perl. Remember, most of the code can be auto-generated from the webapp.
Summary:
1. Genes that are upregulated in Adipose tissue (array express data) → LIST A
2. Those genes from LISTA that interact with PPARG→ LISTB
3. Genes involved in the disease diabetes (omim)→ LISTC
4. Intersect of list B and List C
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MouseMine: Joel Richardson
The InterMine TeamPI: Gos Micklem
Software developers:
Biologist: Rachel Lyne
Julie SullivanSergio ContrinoJoshua HeimbachYo YehudiJustin Clark-Casey
Ex-Team: Richard Smith, Alex Kalderimis, Mike Lyne, Kim Rutherford, Matthew Wakeling, Xavier Watkins, Andrew Varley, Mark Woodbridge, Tom Riley, Peter Mclaren, Debashis Rana, Wenyan Ji, Markus Brosch, Florian Reising, Matthew Chadwick
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The Web Interface
KeywordSearch
TemplateSearches
QueryBuilder
RegionSearch
ResultsTables
ReportPages
List AnalysisPages
Single Item
List
Inputs Search Interfaces Outputs